Use of fluorescent probes to monitor propranolol effects on the murine splenic lymphocyte.

Abstract

Recent studies indicate that propranolol suppresses the normal murine lymphocyte mitogen dose-response(1) and that propranolol has a high affinity for the beta-adrenergic binding site on the murine lymphocyte(2). Since concentrations which suppress the lymphocyte mitogen dose-response are much greater than the Kd for the binding site, it may be suggested that the suppression of the mitogen dose-response is a result of nonspecific effects of propranolol. Three fluorescent probes (1,6-diphenyl-1,3,5-hexatriene (DPH), fluorescein conjugated concanavalin A (F-Con A), and 3,3'-dithio-diisopropyl-oxacarbocyanine iodide (diS-C3-(5)) were used to investigate possible mechanisms of the nonspecific effects of propranolol on the murine splenic lymphocyte. This report presents data which suggests a possible relationship between propranolol concentrations that alter lipid membrane dynamics, as monitored by the fluorescence polarization of DPH, and suppression of the mitogen dose-response in short term cell cultures as effected by propranolol. Also reported are effects of propranolol on the relative mobility of surface membrane lectin receptors as monitored by the fluorescence polarization of F-Con A, effects of propranolol on the transmembrane potential as monitored by fluorescence emission of diS-C3-(5), and the propranolol effect on fluorescence polarization temperature-dependence of DPH and F-Con A. Studies of the effects of sotalol, alprenolol, and metoprolol are included and used for the comparison of different drug effects.